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Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma

Authors
 Prasanta Dey  ;  Ji Yeon Son  ;  Amit Kundu  ;  Kyeong Seok Kim  ;  Yura Lee  ;  Kyungsil Yoon  ;  Sungpil Yoon  ;  Byung Mu Lee  ;  Ki Taek Nam  ;  Hyung Sik Kim 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.20(22) : E5622, 2019 
Journal Title
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 
Issue Date
2019
Keywords
autophagy ; invasion ; metabolism ; migration ; pyruvate kinase M2
Abstract
Emerging evidence indicates that the activity of pyruvate kinase M2 (PKM2) isoform is crucial for the survival of tumor cells. However, the molecular mechanism underlying the function of PKM2 in renal cancer is undetermined. Here, we reveal the overexpression of PKM2 in the proximal tubule of renal tumor tissues from 70 cases of patients with renal carcinoma. The functional role of PKM2 in human renal cancer cells following small-interfering RNA-mediated PKM2 knockdown, which retarded 786-O cell growth was examined. Targeting PKM2 affected the protein kinase B (AKT)/mechanistic target of the rapamycin 1 (mTOR) pathway, and downregulated the expression of glycolytic enzymes, including lactate dehydrogenase A and glucose transporter-1, and other downstream signaling key proteins. PKM2 knockdown changed glycolytic metabolism, mitochondrial function, adenosine triphosphate (ATP) level, and intracellular metabolite formation and significantly reduced 786-O cell migration and invasion. Acridine orange and monodansylcadaverine staining, immunocytochemistry, and immunoblotting analyses revealed the induction of autophagy in renal cancer cells following PKM2 knockdown. This is the first study to indicate PKM2/AKT/mTOR as an important regulatory axis mediating the changes in the metabolism of renal cancer cells.
Files in This Item:
T201905233.pdf Download
DOI
10.3390/ijms20225622
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Nam, Ki Taek(남기택)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174671
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